crossing96/oncoscreening huggingface dataset:
Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation.	Cheliensisin A (Chel A), a styryl-lactone compound extracted from Goniothalamus cheliensis, is reported to have significant anti-cancer effects in various cancer cells. Here we demonstrated that Chel A treatment resulted in apoptosis and an inhibition of anchorage-independent growth in human bladder cancer T24, T24T and U5637 cells. Mechanistic studies showed that such effect is mediated by PH domain and Leucine rich repeat Protein Phosphatases (PHLPP2) protein. Chel A treatment led to PHLPP2 degradation and subsequently increased in c-Jun phosphorylation. Moreover PHLPP2 degradation could be attenuated by inhibition of autophagy, which was mediated by Beclin 1. Collectively, we discover that Chel A treatment induces Beclin-dependent autophagy, consequently mediates PHLPP2 degradation and JNK/C-Jun phosphorylation and activation, further in turn contributing to apoptosis in human bladder cancer cells. Current studies provide a significant insight into understanding of anticancer effect of Chel A in treatment of human bladder cancer.	bladder
Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques.	BACKGROUND: Her2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients' clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients' in Saudi Arabia, and to explore its prognostic value in BC. METHODS: A total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures. RESULTS: IHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient's cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort. CONCLUSION: The study showed that 25 % of our patients' cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.	bladder
[Radical cystectomy in patients with pathological non-muscle invasive bladder cancer].	OBJECTIVE: Carcinoma of bladder is the most common malignancy in the urinary system in China. Most patients with this disease had non-muscle invasive bladder cancer (NMIBC) at the time of diagnosis. Radical cystectomy was indicated for patients with high risk or refractory NMIBC. We aimed to investigate the overall survival and disease-specific survival and related influence factors in patients undergoing radical cystectomy for pathological non-muscle invasive bladder cancer. METHODS: From Jan. 2006 to Dec. 2012, a total of 164 patients with pathological non-muscle invasive bladder cancer underwent radical cystectomy in Peking University First Hospital. Clinical data were retrospectively collected.Incidence of lymph node metastasis and disease recurrence were calculated. The risk factors of disease recurrence were analyzed. Kaplan-Meier plots were used to estimate the overall survival and cancer-specific survival. Multivariate Cox regression analysis was used to evaluate the prognostic factors for survival. RESULTS: Of all the patients included, 159 had T1 disease, and 5 had CIS only. The median follow-up duration was 46.5 months (range: 7-99 months). Fourteen patients were lost during the follow-up. Lymph node metastasis was noted in 6 patients (3.7%), 4 patients had N1 disease, one patient had N2 disease, and one patient had N3 disease. Disease recurrence occurred in 16 patients (9.8%).The most common recurrence sites were the liver, bones, and lungs. The 5-year overall survival and disease-specific survival for all the patients were 85% and 91%, respectively. The patients who underwent pelvic lymph node dissection showed a better prognosis in terms of disease-specific survival than those without (P=0.012). Patients with recurrence harbored a significant poorer survival (P<0.001). According to univariate Cox regression analysis, whether lymph node dissection was performed was an independent risk factor of disease recurrence (P=0.050, OR=2.695, 95%CI 0.999-7.271). In COX regression model, age (P=0.008, OR=1.071, 95%CI 1.018-1.126) and whether lymph node dissection was performed (P=0.011, OR=3.385, 95%CI 1.329-8.621) were related to disease-specific survival. CONCLUSION: Patients with pathological non-muscle invasive bladder cancer underwent early radical cystectomy have a favorable prognosis, and bilateral pelvic lymph node dissection is essential for this procedure as it gains a survival benefit for the patients.	bladder
Validation of Preoperative Risk Grouping of the Selection of Patients Most Likely to Benefit From Neoadjuvant Chemotherapy Before Radical Cystectomy.	INTRODUCTION: The aim of this study was to validate the value of preoperative patient characteristics in prognosticating survival after radical cystectomy (RC) to guide treatment decisions regarding neoadjuvant systemic treatment. METHODS: We evaluated a single cohort of 449 consecutive patients treated with RC for bladder cancer. Patients treated with neoadjuvant therapy were excluded from the study cohort (n = 24). Patients were stratified based on preoperative characteristics into 2 risk groups. The high-risk group included patients harboring clinically non-organ-confined disease (≥ cT3), hydroureteronephrosis, lymphovascular invasion, or variant histology (micropapillary, neuroendocrine, sarcomatoid, or plasmacytoid variants on transurethral resection). The low-risk group included patients with cT2 disease without any of the aforementioned features. Survival expectancies after surgery were evaluated using competing risk and Kaplan-Meier analyses. RESULTS: We identified 153 (44.6%) low-risk and 190 (55.4%) high-risk patients. The majority of high-risk patients had only 1 high-risk feature (n = 111; 58.4%); the most common high-risk feature was preoperative hydroureteronephrosis (n = 107; 56.3%). The majority of low-risk patients were upstaged at time of RC (n = 118; 70.6%), whereas a pathologic downstage occurred only in 27 high-risk patients (14.2%). Cancer-specific mortality-free rates at 5 years after RC were 77.4% versus 64.4% for low-risk versus high-risk patients, respectively. CONCLUSIONS: We confirm that preoperative risk features can stratify patients with muscle-invasive bladder cancer into differential risk groups regarding survival. Decision-making regarding neoadjuvant systemic therapy administration is likely to be improved by integrating clinical stage, lymphovascular invasion, variant histology, and hydroureteronephrosis.	bladder
The Emerging Molecular Landscape of Urothelial Carcinoma.	Although there have been many recent discoveries in the molecular alterations associated with urothelial carcinoma, current understanding of this disease lags behind many other malignancies. Historically, a two-pathway model had been applied to distinguish low- and high-grade urothelial carcinoma, although significant overlap and increasing complexity of molecular alterations has been recently described. In many cases, mutations in HRAS and FGFR3 that affect the MAPK and PI3K pathways seem to be associated with noninvasive low-grade papillary tumors, whereas mutations in TP53 and RB that affect the G1-S transition of the cell cycle are associated with high-grade in situ and invasive carcinoma. However, recent large-scale analyses have identified overlap in these pathways relative to morphology, and in addition, many other variants in a wide variety of oncogenes and tumor-suppressor genes have been identified. New technologies including next-generation sequencing have enabled more detailed analysis of urothelial carcinoma, and several groups have proposed molecular classification systems based on these data, although consensus is elusive. This article reviews the current understanding of alterations affecting oncogenes and tumor-suppressor genes associated with urothelial carcinoma, and their application in the context of morphology and classification schema.	bladder
Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients.	PURPOSE: Treatments with cancer vaccines may be delivered as combination therapies for better efficacy. Addition of intravesical immunostimulation with bacteria promotes vaccine-specific T cells in the bladder and tumor-regression in murine bladder cancer models. Here, we determined whether an adjuvanted cancer vaccine can be safely administered with concomitant standard intravesical Bacillus-Calmette-Guérin (BCG) therapy and how vaccine-specific immune responses may be modulated in patients with non-muscle-invasive bladder cancer (NMIBC). EXPERIMENTAL DESIGN: In a nonrandomized phase I open-label exploratory study, 24 NMIBC patients, apportioned in three groups, received 5 injections of a subunit cancer vaccine (recMAGE-A3 protein+AS15) alone or in two combinations of intravesical BCG-instillations. Safety profiles were compared between the three treatment groups, considering single vaccine injections or BCG instillations and concomitant interventions. Immune responses in blood and urine were compared between treatment groups and upon BCG instillations. RESULTS: The mild adverse events (AE) experienced by all the patients were similar to AE previously reported for this vaccine and standard BCG treatment. AEs were not increased by the double interventions, suggesting that BCG did not exacerbate the AE caused by the MAGE-A3 vaccine and vice-versa. All patients seroconverted after MAGE-A3 vaccination. In half of the patients, vaccine-specific T cells were induced in blood, irrespective of BCG treatment. Interestingly, such T cells were only detected in urine upon BCG-induced T-cell infiltration. CONCLUSIONS: Cancer vaccines, including strong adjuvants, can be safely combined with intravesical BCG therapy. The increase of vaccine-specific T cells in the bladder upon BCG provides proof-of-principle evidence that cancer vaccines with local immunostimulation may be beneficial. Clin Cancer Res; 23(3); 717-25. ©2016 AACR.	bladder
Krüppel-like factor 4 is a novel prognostic predictor for urothelial carcinoma of bladder and it regulates TWIST1-mediated epithelial-mesenchymal transition.	BACKGROUND: Krüppel-like factor 4 (KLF4) exerts tumor suppressive or oncogenic functions in a cell-type-dependent manner, but its prognostic role in urothelial carcinoma of bladder (UCB) remains unclear. We aimed to determine how KLF4 regulates epithelial-mesenchymal transition (EMT) and predicts patient survival in UCB. PATIENTS AND METHODS: The roles of KLF4 and other EMT regulators in cancer progression were studied in UCB specimens of 398 patients, UCB cell lines. The results were validated by open-access The Cancer Genome Atlas dataset. RESULTS: Over a median follow-up of 46.5 months, tissue microarray demonstrated that strong KLF4 expression was associated with higher risk toward metastasis and death (P<0.001). KLF4 expression positively correlated with TWIST1 and vimentin, and inversely correlated with E-cadherin expression. Metastasis-free survival was poorest in KLF4/TWIST1 coexpression group, followed by KLF4 or TWIST1 expression-alone group, and no-expression group (P<0.001). Multivariate analysis substantiated that KLF4/TWIST1 coexpression independently predicted overall mortality and metastasis risk with hazard ratios of 2.43 (95% CI: 1.65-3.64) and 7.54 (CI: 4.03-12.10). The Cancer Genome Atlas dataset of bladder cancer also revealed a trend toward decreased overall survival in the high KLF4 expression group as compared to the low KLF4 group. In vitro, KLF4 is accompanied with decreased E-cadherin and β-catenin expressions, increased vimentin and fibronectin expressions, and enhanced migration/invasion. KLF4 knockdown suppressed TWIST1 expression and inhibited EMT, migration and invasion, whereas enforced KLF4 overexpression activated TWIST1 expression and restored EMT and metastatic phenotype. Furthermore, TWIST1 knockdown abolished KLF4-faciliated EMT and metastatic feature without affecting KLF4 expression. CONCLUSIONS: KLF4 promotes TWIST1-mediated EMT and may represent a novel prognostic predictor in UCB.	bladder
The clinical value of PSA increase during intravesical adjuvant therapy for nonmuscle-invasive bladder cancer.	INTRODUCTION: Prostatic Specific Antigen (PSA), Bacillus Calmette-Guerin (BCG) increase after intravesical BCG has been reported. The need of prostate biopsy in these patients is object of debate. The aim of our study was to evaluate the effect of intravesical therapy on PSA after transurethral resection (TUR) of nonmuscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Patients undergoing intravesical chemotherapy or immunotherapy for NMIBC were entered. PSA was measured before TUR, before the first and after the sixth instillation, 30 and 90 days after the last instillation. Patients with PSA ≥4 ng/ml or palpable prostate nodule were excluded. RESULTS: Out of 130 patients, 105 were evaluable. PSA increase (mean: 7.15 ng/ml) was detected after TUR and before intravesical therapy in 14 patients (13.3%). Of the remaining 91 patients, 65 (71.4%) received chemotherapy and 26 (28.6%) BCG. Median PSA before and during therapy was 1.80 and 1.97 ng/ml, with a 36% median increase in 66 patients (72.5%) (p = 0.13). No statistically significant difference emerged between chemotherapy and BCG (p = 0.22). PSA higher than 4 ng/ml was detected in six (6.3%) and two (2.1%) patients after chemotherapy and BCG, respectively, and was no more evident at 90 days. DISCUSSION: PSA increase due to intravesical therapy is rare and usually not clinically significant. PSA rising above 4 ng/ml during intravesical treatment was evident only in 8% of patients. PSA before TUR should be available and considered as the basal value. Elevated PSA detected during therapy should be monitored and biopsy proposed only if persisting more than 3 months after the end.	bladder
Clinical predictors for high-grade bladder cancer before first-time transurethral resection of the bladder tumor: a retrospective cohort study.	The aim of this study was to identify the clinical predictors related to the risk of high-grade bladder cancer before first-time transurethral resection of the bladder tumor (TUR-Bt) and to externally validate the accuracy of Shapur's nomogram predicting the risk of high-grade bladder cancer in Japanese patients. As a result, episode of gross hematuria (odds ratio: 2.68, P = 0.02), larger tumor size (odds ratio: 1.89, P < 0.01) and positive urinary cytology (odds ratio: 8.34, P < 0.01) were found to be significant predictors for high-grade bladder cancer. Furthermore, the nomogram showed a high predictive accuracy in our Japanese population (area under the curve: 0.79). Clinicians will be able to predict high-grade bladder cancer using the common factors in Shapur's study and ours, such as tumor size and urinary cytology, and gross hematuria as the additional factor first identified here to decide priorities for the treatment of patients diagnosed with bladder cancer.	bladder
Impact of Glycemic Control and Metformin Use on the Recurrence and Progression of Non-Muscle Invasive Bladder Cancer in Patients with Diabetes Mellitus.	The purpose of the present study was to determine the potential relationships of glycemic control and use of metformin with non-muscle invasive bladder cancer characteristics. We reviewed data from 645 patients with non-muscle invasive bladder cancer between January 2004 and May 2015. We analyzed the association of pre and post-operative glycemic control and use of metformin with clinical characteristics of bladder tumors. We also analyzed the association of glycemic control and use of metformin with recurrence-free and progression-free survivals. Diabetes mellitus patients showed decreased recurrence-free survival (hazard ratio 1.42; 95% confidence interval 1.1-1.9; P = 0.021) and progression-free survival (hazard ratio 1.79; 95% confidence interval 1.1-2.8; P = 0.013). Diabetes mellitus patients with a HbA1c ≥ 7.0% demonstrated a higher rate of progression (P = 0.026). Kaplan-Meier analysis showed that progression-free survival rate was associated with poor baseline glycemic control (P = 0.026) and post-operative glycemic control (P = 0.025). However, use of metformin had no impact on the recurrence (P = 1.00) and progression (P = 0.282). In conclusion, poor baseline and post-operative glycemic control was related with shorter progression-free survival of patients with non-muscle invasive bladder cancer. Use of metformin had no impact on the recurrence and progression. Therefore, tight glycemic control and close follow-up for bladder tumor may be beneficial in patients with poor glycemic control.	bladder
Suppressed Recurrent Bladder Cancer after Androgen Suppression with Androgen Deprivation Therapy or 5α-Reductase Inhibitor.	PURPOSE: We determined whether intravesical recurrence is affected by inhibition of androgen signaling among men with nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We examined the intravesical recurrence rate among men treated with or without androgen suppression therapy by androgen deprivation therapy for prostate cancer or 5α-reductase inhibitor dutasteride for benign prostatic hyperplasia. RESULTS: We studied 228 men, including 32 with and 196 without androgen suppression therapy. During a median followup of 3.6 and 3.0 years intravesical recurrence developed in 4 (12.5%) and 59 men (30.1%) with and without androgen suppression therapy, respectively. On multivariate analysis multiple tumors (HR 1.82, p = 0.027), a large tumor (HR 2.13, p = 0.043) and ever smoking (HR 2.45, p = 0.020) as well as the presence of androgen suppression therapy (HR 0.36, p = 0.024) were independent risk factors for intravesical recurrence. Notably, tumor progressed to muscle invasive bladder cancer in 6 men (3.1%) without androgen suppression therapy. No man with androgen suppression therapy progressed to muscle invasive bladder cancer. CONCLUSIONS: Our study suggests the possibility of androgen suppression therapy as prophylaxis for intravesical recurrence of bladder cancer. Further explorations are warranted of the prophylactic effect of androgen suppression therapy on bladder cancer pathogenesis.	bladder
Fluoxetine regulates cell growth inhibition of interferon-α.	Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase. Activations and signal transducer and transactivator (STAT)-1 and peroxisome proliferator-activated receptor alpha (PPAR-α) were involved in this process. Chemical inhibitions of STAT-1 or PPAR-α partially rescued bladder carcinoma cells from IFN-α-mediated growth inhibition via blockades of G1 arrest, cyclin D1 reduction, p53 downregulation and p27 upregulation in the presence of fluoxetine. However, the functions of both proteins were not involved in the control of fluoxetine over apoptosis and maintained the declined G2/M phase of IFN-α. These results indicated that activation of PPAR-α and STAT-1 participated, at least in part, in growth inhibition of IFN-α in the presence of fluoxetine.	bladder
Pheochromocytoma of the urinary bladder--A case report.	INTRODUCTION: Pheochromocytoma of the urinary bladder is a rare tumor and presents less than 0.06% of all urinary bladder tumors. CASE REPORT: We presented a 49-year-old female patient with a history of daily paroxysmal hypertension accompanied with flushing of the face and upper chest, palpitations and excessive sweating prior to micturition. Ultrasonography reported a 3 cm bladder wall tumor. The 131I-metaiodobenzylguanidine (131I-MIBG) scan showed a pathological isotope accumulation in the projection of the bladder. The patient underwent a partial cystectomy. One year following the operation the patient was normotensive and without recurrence. CONCLUSION: The most efficient treatment option for bladder pheochromocytoma is surgical resection. The most important fact in the diagnostics is suspicion on this rare condition.	bladder
[Short version of the German S3 guideline for bladder cancer].	Urinary bladder cancer is the second most common cancer of the urogenital system. The Guideline Program in Oncology (Leitlinienprogramm Onkologie) of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF), the German Cancer Society (Deutsche Krebsgesellschaft) and the German Cancer Aid (Deutsche Krebshilfe) as well as 31 different medical societies have developed the first interdisciplinary, evidence-based German guideline for bladder cancer. This short version presents the resulting series of diagnostic and therapeutic recommendations which were based on a systematic literature search and approved by a team of bladder cancer experts. The full version is available under http://leitlinienprogramm-onkologie.de/ .	bladder
High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical BCG Shortage.	Bladder cancer is the second commonest urinary tract malignancy with 70-80 % being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC (T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin (BCG) is commonly used as first line therapy in this patient group but there is a current worldwide shortage. BCG has been shown to reduce recurrence in high-risk NMIBC and is more effective that other intravesical agents including mitomycin C, epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high change of cure in this cohort (80-90 %) and is a more radical treatment option which patients need to be counselled carefully about. Bladder thermotherapy and electromotive drug administration with mitomycin C are alternative therapies with promising short-term results although long-term follow-up data are lacking.	bladder